This is an application for a K23 award for Dr. Hiroyu Hatano, a fellow in adult infectious diseases at the University of California, San Francisco who is establishing herself as a young investigator in patient-oriented translational research of HIV-infected elite controllers. Elite controllers are HIV-antibody individuals who have maintained "undetectable" plasma HIV-1 RNA levels in the absence of antiretroviral therapy. This K23 award will provide Dr. Hatano with the support necessary to accomplish the following goals: (1) to recover, quantify, and characterize HIV in elite controllers;(2) to examine the interactions between host and virologic factors that contribute to effective virologic control in elite controllers;and (4) to develop an independent, clinic-based translational research career. To achieve these goals, Dr. Hatano has assembled a mentoring team comprised of her primary mentor, Dr. Steven G. Deeks, an expert in translational HIV research with a focus on HIV pathogenesis, and three co-mentors: Dr. Joseph K. Wong, a clinical virologist and expert in HIV latency;Dr. Joseph (Mike) McCune, an immunologist with expertise in the immunology of HIV infection;and Dr. Jeffrey N. Martin, an expert in infectious diseases and epidemiology. Although highly active antiretroviral therapy (HAART) has been effective in decreasing the morbidity and mortality associated with HIV infection for patients with access to medical care, the challenges of long-term efficacy, toxicity, cost, and life-long adherence remain. Thus, models of eradication need to be examined in order to elucidate potential host and viral factors that may make eradication possible. One such model is the elite controller cohort. Although rare, elite controllers provide a unique opportunity to study a naturally occurring model of sustained control of HIV. Dr. Hatano will identify both virologic factors (Aim 1) and host factors (and their interactions) (Aim 2) that contribute to the effective control of HIV in elite controllers, and she will examine whether a proportion of them have "cleared" their HIV infection (Aim 3). This research will provide Dr. Hatano with the skills and preliminary data to successfully compete for R34 (Year 4) and U01 (Year 5) NIH grant support that will focus specifically on HIV latency and control of HIV in elite controllers and whether treatment with HAART or others methods aimed at depletion of HIV can eradicate HIV in elite controllers. Public health relevance: Insight into how elite controllers maintain their distinctive version of HIV latency and durable viral control may affect HIV treatment strategies, bolster therapeutic vaccine design efforts, and contribute to the possible eradication of HIV.